The Role of Renal Progenitors and Polyploid Tubular Cell Response in Glomerular and Tubular Diseases

Nephropathy Clinical Trial

Official title:

Studying the Role of Renal Progenitors and Polyploid Tubular Cell Response in Glomerular and Tubular Diseases: Analysis on Renal Biopsies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06325059
• Other study ID #: BIO-KIDNEY
• Status: Recruiting
• Phase: N/A
• Start date: March 22, 2023
• Est. completion date: November 30, 2047

Study information

• Verified date: March 2024
• Source: Meyer Children's Hospital IRCCS
• Contact: Paola Romagnani, MD
• Phone: 055 5662562
• Email: paola.romagnani[@]meyer.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Renal progenitors are a subset of parietal epithelial cells (PECs) localized at the urinary pole of Bowman's capsule. Experimental models of podocyte damage showed that PECs can potentially regenerate lost podocytes by migrating from Bowman's capsule to the glomerular tuft, acquiring the morphological and functional features of mature podocytes. Podocyte loss and damage, as well as the inability of PECs to replace lost podocytes, lead to glomerular scarring and chronic kidney disease (CKD) progression.

In addition, the investigators of the present study and others have recently demonstrated the existence of a specific subpopulation of tubular cells in the human kidney with a high potential for regeneration and resistance to death, thus acting as tubular progenitors. These cells are involved in tubular response to damage during acute kidney injury (AKI) trough endoreplication (polyploidization).

Kidney biopsy is the cornerstone of diagnosis in many kidney diseases leading to CKD and AKI, allowing unambiguous diagnosis in some cases and presumptive diagnosis of ongoing disease in others. Very recently, super resolution imaging techniques proved to maintain current diagnostic standards while allowing to study morphological features of pathophysiological mechanisms of glomerular and tubular diseases.

The rationale of this project is to study the role of renal progenitors (PECs and tubular progenitors) in the pathogenesis of CKD and AKI trough super resolution imaging applied to human renal biopsies, to the aim of identifying relevant connections with clinical data and markers of damage and/or disease progression.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: November 30, 2047
• Est. primary completion date: March 22, 2047
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 17 Years

Eligibility

Inclusion Criteria:

• Patients with glomerular diseases undergoing renal biopsy (e.g., rapidly progressive glomerulonephritis, minimal change disease, focal segmental glomerulosclerosis, diabetic nephropathy, lupus nephritis, membranous nephropathy, IgA nephropathy, etc)

• Patients with AKI, regardless of the nature of the damage (septal, ischemic, toxic, or unknown).

• Signed informed consent form

Exclusion Criteria:

• Sample insufficient and/or unavailable

Related Conditions & MeSH terms

• Nephropathy

Intervention

Other:
• Study of renal progenitors
Evaluation of the role of renal progenitors in pathogenesis and mechanisms of disease progression in kidney biopsies performed for diagnostic purposes

Locations

Country	Name	City	State
Italy	Meyer Children's Hospital IRCCS	Firenze

Sponsors (1)

Lead Sponsor	Collaborator
Meyer Children's Hospital IRCCS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of the role of renal progenitors in the progression of glomerular diseases	The presence renal progenitors will be assessed by immunofluorescence and confocal microscopy on histological sections from renal biopsy performed for diagnostic purposes.; The following features will be assessed and correlated with clinical parameters of renal function: number of renal progenitors (CD133+CD24+CD106+ cells/section); number of podocyte progenitors (CD133+WT1+, CD24+synaptopodin, CD24+podocin+ cells/section); number of activated progenitors in the Bowman's capsule (CD133+SFN+/section); quantitative and semiqualitative analysis of the slit diaphragm; presence and characterization of immune complexes	Clinical data will be collected at enrollment (kidney biopsy) and at 3, 6 and 12 months from enrollment, then annually until the end of the study (up to 9 years)
Secondary	Evaluation of the role of tubular endoreplication in mechanisms of acute kidney injury (AKI)	The presence of tubular progenitors will be assessed by immunofluorescence and confocal microscopy evaluation on histological sections from renal biopsy performed for diagnostic purposes. The presence of polyploid tubular cells will be assessed using specific markers.; In particular, the following features will be assessed: number of tubular progenitors (CD133+CD24+CD106- cells) over the total of tubular cells (phaIIoidin+, AQP1+, THP+, AQP2+ cells); number of Ki-67+ or PCNA+ over the total of tubular cells (%); number of polyploid tubular cells (CDK4+ or CDT1+ and p-H3+) over the total of tubular cells;	Clinical data will be collected at enrollment (kidney biopsy) and at 3, 6 and 12 months from enrollment, then annually until the end of the study (up to 9 years)
Secondary	Evaluation of the role of tubular endoreplication in mechanisms of acute kidney injury (AKI) trough DNA and RNA analysis	The presence of tubular progenitors will be assessed by immunofluorescence and confocal microscopy evaluation on histological sections from renal biopsy performed for diagnostic purposes. The presence of polyploid tubular cells will be assessed using specific markers, in particular: DNA content (fluorescence intensity of Picogreen/YAP1 staining); RNA expression of polyploidy markers (TMSB10, SEMA5a, VCAM1, BIRC5, AKT, E2F7, E2F8, CDK1, CCNB1)	Clinical data will be collected at enrollment (kidney biopsy) and at 3, 6 and 12 months from enrollment, then annually until the end of the study (up to 9 years)